Let me try another tact here to answer this question...
Exchange 2000 & 2003:
Information Store: Back this up ALWAYS! This will allow you to recover your database in the event of a disaster, as well as allowing you to restore ALL mailboxes (all at once that is)
Mailboxes: Back the Mailbox resource up in a seperate job if you will ever want to restore INDIVIDUAL mailboxes or messages. This is the only way to do individual restores. An Information Store restore will restore ALL mailboxes as part of the database restore.
For mailbox backups, you can use global excludes (** wildcard) to specify folders in all mailboxes not to be backed up. This is very useful to specify the Delete Items and Sent Items folders from all users since it will make the backups that much faster since there is less to backup. However, it is all up to you and if time is no issue, just do a full backup of mailboxes (no excludes) one a week, and incremental and differentials the other 6 days.
Backing up Mailboxes will backup all contacts, appointments, journals, etc. Nothing needs to be set up in Exchange.
Exchange 5.5
If you only backup you IS, then you could be in a world of hurt later. In 5.5 you need to back up the IS AND the DS (Directory). In 2000/2003 those two are combined to make the Information Store, but in 5.5 they are seperate.
Other than that, the mailbox type issues are all the same as noted above for 2000/2003.
Always make the IS (or IS/DS) seperate jobs. THere is nothing wrong with putting them together, but it is much easier to schedule and plan backup windows better if they are seperate. An Information Store backup will be MUCH faster than a mailbox backup. Putting them together will make for one long job! The mailbox backup is slow due to limitations of MAPI and how backups have to read each message.
Hope that clarifies thiggns a little bit.